3,210 research outputs found
Comprehensive translocation and clonality detection in lymphoproliferative disorders by next generation sequencing
The orientation and kinematics of inner tidal tails around dwarf galaxies orbiting the Milky Way
Using high-resolution collisionless N-body simulations we study the
properties of tidal tails formed in the immediate vicinity of a two-component
dwarf galaxy evolving in a static potential of the Milky Way (MW). The stellar
component of the dwarf is initially in the form of a disk and the galaxy is
placed on an eccentric orbit motivated by CDM-based cosmological simulations.
We measure the orientation, density and velocity distribution of the stars in
the tails. Due to the geometry of the orbit, in the vicinity of the dwarf,
where the tails are densest and therefore most likely to be detectable, they
are typically oriented towards the MW and not along the orbit. We report on an
interesting phenomenon of `tidal tail flipping': on the way from the pericentre
to the apocentre the old tails following the orbit are dissolved and new ones
pointing towards the MW are formed over a short timescale. We also find a tight
linear relation between the velocity of stars in the tidal tails and their
distance from the dwarf. Using mock data sets we demonstrate that if dwarf
spheroidal (dSph) galaxies in the vicinity of the MW are tidally affected their
kinematic samples are very likely contaminated by tidally stripped stars which
tend to artificially inflate the measured velocity dispersion. The effect is
stronger for dwarfs on their way from the peri- to the apocentre due to the
formation of new tidal tails after pericentre. Realistic mass estimates of dSph
galaxies thus require removal of these stars from kinematic samples.Comment: 8 pages, 7 figures, accepted for publication in MNRA
Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota
Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may
modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We
hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals.
Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes.
Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected
children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition.
Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies
Shotgun Proteomics Identifies Serum Fibronectin as a Candidate Diagnostic Biomarker for Inclusion in Future Multiplex Tests for Ectopic Pregnancy
Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when 'ambiguous' medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests
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Comparative prebiotic activity of mixtures of cereal grain polysaccharides
The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential
Epileptic networks in focal cortical dysplasia revealed using electroencephalography-functional magnetic resonance imaging.
Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome
R-process enrichment from a single event in an ancient dwarf galaxy
Elements heavier than zinc are synthesized through the (r)apid and (s)low
neutron-capture processes. The main site of production of the r-process
elements (such as europium) has been debated for nearly 60 years. Initial
studies of chemical abundance trends in old Milky Way halo stars suggested
continual r-process production, in sites like core-collapse supernovae. But
evidence from the local Universe favors r-process production mainly during rare
events, such as neutron star mergers. The appearance of a europium abundance
plateau in some dwarf spheroidal galaxies has been suggested as evidence for
rare r-process enrichment in the early Universe, but only under the assumption
of no gas accretion into the dwarf galaxies. Cosmologically motivated gas
accretion favors continual r-process enrichment in these systems. Furthermore,
the universal r-process pattern has not been cleanly identified in dwarf
spheroidals. The smaller, chemically simpler, and more ancient ultra-faint
dwarf galaxies assembled shortly after the first stars formed, and are ideal
systems with which to study nucleosynthesis events such as the r-process.
Reticulum II is one such galaxy. The abundances of non-neutron-capture elements
in this galaxy (and others like it) are similar to those of other old stars.
Here, we report that seven of nine stars in Reticulum II observed with
high-resolution spectroscopy show strong enhancements in heavy neutron-capture
elements, with abundances that follow the universal r-process pattern above
barium. The enhancement in this "r-process galaxy" is 2-3 orders of magnitude
higher than that detected in any other ultra-faint dwarf galaxy. This implies
that a single rare event produced the r-process material in Reticulum II. The
r-process yield and event rate are incompatible with ordinary core-collapse
supernovae, but consistent with other possible sites, such as neutron star
mergers.Comment: Published in Nature, 21 Mar 2016:
http://dx.doi.org/10.1038/nature1742
Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage
Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.- Background - Results -- Authentication of a preserved oral biofilm in calculus samples -- Dental calculus and plaque biofilm communities are distinct -- Health-associated communities of dental plaque and calculus are distinct -- Signatures of health and of disease are shared in modern and historic calculus samples -- Microbial community differences between health and disease in calculus are poorly resolved -- Absence of caries-specific microbial profiles in dental calculus -- Microbial co-exclusion patterns in plaque and calculus reflect biofilm maturity -- Microbial complexes in plaque and calculus -- Functional prediction in calculus is poorly predictive of health status -- Proteomic profiles of historic healthy site calculus -- Correlations between taxonomic, proteomic, and metabolomic profiles - Discussion - Conclusions - Materials and methods --Historic and modern calculus sample collection DNA extraction -- DNA library construction and high-throughput sequencing -- DNA sequence processing -- Genetic assessment of historic calculus sample preservation -- Genetic microbial taxonomic profiling -- Principal component analysis -- Assessment of differentially abundant taxa -- Sparse partial least squares-discriminant analysis -- Assessment of microbial co-exclusion patterns -- Gene functional categorization with SEED -- Proteomics -- Metabolomics -- Regularized canonical correlation analysi
Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression
Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe
Measurement of Scintillation and Ionization Yield and Scintillation Pulse Shape from Nuclear Recoils in Liquid Argon
We have measured the scintillation and ionization yield of recoiling nuclei
in liquid argon as a function of applied electric field by exposing a
dual-phase liquid argon time projection chamber (LAr-TPC) to a low energy
pulsed narrow band neutron beam produced at the Notre Dame Institute for
Structure and Nuclear Astrophysics. Liquid scintillation counters were arranged
to detect and identify neutrons scattered in the TPC and to select the energy
of the recoiling nuclei. We report measurements of the scintillation yields for
nuclear recoils with energies from 10.3 to 57.3 keV and for median applied
electric fields from 0 to 970 V/cm. For the ionization yields, we report
measurements from 16.9 to 57.3 keV and for electric fields from 96.4 to 486
V/cm. We also report the observation of an anticorrelation between
scintillation and ionization from nuclear recoils, which is similar to the
anticorrelation between scintillation and ionization from electron recoils.
Assuming that the energy loss partitions into excitons and ion pairs from
Kr internal conversion electrons is comparable to that from Bi
conversion electrons, we obtained the numbers of excitons () and ion
pairs () and their ratio () produced by nuclear recoils from
16.9 to 57.3 keV. Motivated by arguments suggesting direction sensitivity in
LAr-TPC signals due to columnar recombination, a comparison of the light and
charge yield of recoils parallel and perpendicular to the applied electric
field is presented for the first time.Comment: v2 to reflect published versio
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